Cancer continues to be one of the foremost health problems. Conventional treatments such as surgery and chemotherapy have been extremely successful in certain cases; in other instances, much less so. Radiation therapy has also exhibited favorable results in many cases, while failing to be completely satisfactory and effective in all instances. It has been proposed that an alternative form of radiation therapy, known as microbeam radiation therapy (MRT) or microbeam radiosurgery (MBRS) may be used to treat certain tumors for which the conventional methods have been ineffective.
MRT or BMRS, hereafter designated MBRS, differs from conventional radiation therapy by employing multiple parallel fan beams of radiation with a narrow dimension or thickness that may be on the order of 10 to 200 micrometers. The thickness of the microbeams is dependent upon the capacity of tissue surrounding a beam path to support the recovery of the tissue injured by the beam. It has been found in experimental rodents that certain types of cells, notably endothelial cells lining blood vessels, but also oligodendroglial and other supporting cells, have the capacity to migrate over microscopic distances, infiltrating tissue damaged by radiation and reducing tissue necrosis in the beam path. In MBRS, sufficient unirradiated or minimally irradiated microscopic zones remain in the normal tissue but not in neoplastic tissue through which the microbeams pass to allow efficient repair of irradiation-damaged normal tissue. As a result, unidirectional MBRS is, fundamentally, greatly different from other forms of radiation therapy, while multidirectional, stereotactic MBRS is substantially different from other forms of stereotactic radiotherapy.
In conventional clinical forms of radiation therapy, including the radiosurgical techniques employing, steeotactically, multiple, slender, convergent beams of X-ray or gamma radiation, each beam is usually at least five hundred micrometers wide, so that the otherwise potential biological advantage of rapid repair by migrating or proliferating endothelial cells is minimal or nonexistent. Observations of the regeneration of blood vessels following MBRS indicate that endothelial cells cannot efficiently regenerate damaged blood vessels over distances on the order of more than 100 micrometers (μm). Thus, in view of this knowledge concerning radiation pathology of normal blood vessels, the skilled artisan may select a microbeam thickness as small as 20 μm but not more than 100 μm. Further, the microbeams may include substantially parallel, non-overlapping, planar beams with center-to-center spacing of from about 50 μm to about 500 μm. Also, the microbeam energies should be confined to the range from about 30 to several hundred keV, lest tissue penetration from lower energies be inadequate on one hand and lateral scattering of radiation from the high-dose in-beam path excessively increase the dose between microbeams, thereby obviating the microbeam normal-tissue-protective effect on the other hand. These microbeams result in a dosage profile with microscopically narrow (generally less than 100 μm wide) peaks and submillimeter-wide (generally less than a half-millimeter wide) valleys between them. The region between the peaks is called the valley region. The radiation dosage is large enough to render all cells in the targeted malignancy within the peak-zone slice non-clonogenic, but renders normal cells within the peak-zone slice proximal and distal to a targeted malignancy similarly non-clonogenic. The critical and novel therapeutic aspect of MBRS is that such damage proximal and distal to the malignancy is largely repaired by the influx of surviving progenitor cells from adjacent zones of low-dose normal tissue in the valleys. However, such damage to the targeted malignancy is therapeutically largely not repaired, putatively because the valley regions in the malignancy do not communicate well biologically with zones of cell loss in the nearby peak-dose regions of the same malignancy. Presumably, such lack of communication, especially among supporting cells of the malignancy, therapeutically impairs the viability and growth potential of the malignancy. The minimum radiation dosage in the valleys (i.e., the “nadir” valley dosage) must be just small enough to prevent clonogenically lethal damage to some necessary fraction of potentially reparative cells in the valley dosage areas . . . but not smaller than necessary for optimal peak-dose damage to the malignancy, since a nadir valley dose is roughly arithmetically proportional to the arithmetic average of the pair of doses in the adjacent peaks.
A division of a radiation beam into microbeams and the use of a patient-exposure plan that provides non-overlapping beams in the tissue surrounding the target tumor allows the non-target tissue to recover from the radiation injury, in particular by migration of regenerating endothelial and other reparative cells of the small blood vessels to the areas in which the endothelial cells have been injured beyond recovery. Therefore, the probability of radiation-induced coagulative necrosis in normal, non-targeted tissue is lowered, which may improve the effectiveness of clinical radiation therapy for deep-seated and/or superficially situated tumors.
Various studies have shown the microbeam tissue-sparing effect for X-ray microbeams. Although other methods and processes are known for radiation therapy, none provides a method for performing radiation therapy while avoiding significant radiation-induced damage to tissues proximal to, distal to, and interspersed with the targeted lesion.
Present radiation therapies often take many days and weeks of treatment to provide enough radiation to a target tumor. On the other hand, MBRS can provide an effectual treatment in single visit. Very high (or lesser but sufficiently high-) energy radiation may be used with MBRS that results in the destruction of tumor tissue while allowing for the regeneration of healthy tissue adversely affected by the microbeams.
Further, MBRS provides a method for treating cancerous tumors by using extremely narrow, quasi-parallel X-ray microbeams increasing the precision and accuracy of radiation therapy. MBRS also provides a method of using extremely small microbeams of radiation to unexpectedly produce effective radiation therapy while avoiding significant radiation-induced damage to non-targeted tissues.
A major benefit of MBRS is that the microbeams are so narrow that the vasculature of the tissue and other components of the tissue through which the microbeams pass can repair themselves by the infiltration of endothelial cells and other cells from surrounding unirradiated tissue. Present knowledge indicates that such infiltration can take place only over distances on the order of less than 500 μm, that specific distance depending on the specific kind of tissue being irradiated. The dimensions of the microbeams and the configuration of the microbeam array are therefore determinable with reference to the susceptibility to irradiation of the target tissue and the surrounding tissue to irradiation and the capacities of the various involved tissues to regenerate.
U.S. Pat. No. 5,339,247 to Slatkin et al. titled Method for Microbeam Radiation Therapy provides background related to MBRS, and is hereby incorporated by reference for all purposes as if fully set forth herein.